Systematic review on the efficacy and safety of injectable bulking agents for passive faecal incontinence

Luo C, Samaranayake CB, Plank LD, Bissett IP

CRD summary

The review concluded there was little evidence for the effectiveness in managing passive faecal incontinence in adults with injectable bulking agents; however they appeared safe, with only minor adverse events. The authors' conclusions reflected the evidence presented, but the reliability of the conclusions is uncertain due to the poor quality evidence included in the review.

Authors' objectives

To determine the efficacy and safety of injectable bulking agents in adults with passive faecal incontinence.

Searching

PubMed, EMBASE, Scopus, the Cochrane Library and Web of Knowledge were searched without language restriction for studies published after 1990 (exact search dates were not reported). Search terms were reported. In addition, a number of registries of current clinical trials and relevant conference proceedings were searched to 2007. Reference lists of relevant reviews and included studies were also searched. Cited unpublished studies were followed up through targeted electronic searches and communication with relevant authors.

Study selection

Trials that included more than ten adults receiving injectable bulking agent for passive faecal incontinence were eligible for inclusion. Eligible trials had to assess preoperative and postoperative incontinence using a validated measure. Primary outcomes were faecal incontinence, anal manometry, quality of life (QoL), adverse events and safety.

Half the included studies used PTQ (silicone biomaterial) as the injectable bulking agent (unspecified, with or without ultrasound guidance); the remaining studies used Coaptite, Contigen, Durasphere and ethylene vinyl alcohol (EVOH). Injection methods, volume and number of injections varied between studies. The sole controlled trial compared PTQ bulking agent with placebo. Faecal incontinence was assessed using various validated scores (details reported in review). Participants were aged from 22 to 87 years.

Two reviewers independently selected studies for inclusion; differences were resolved through discussion and consensus.

Assessment of study quality

Validity of case series were assessed using a tool adapted from Taylor et al to provide an overall rating based on patient selection, prospective cases, additional co-interventions, losses to follow-up, and consistency of delivery of intervention. The maximum possible score was 5.

It appeared that validity was assessed independently by two reviewers.

Data extraction

Data were extracted on preoperative and postoperative faecal incontinence scores and used to calculate the mean percentage change. Data on quality of life were also extracted. Where necessary authors were contacted for missing data.

Two reviewers independently extracted data.

Methods of synthesis

The weighted mean percentage change in faecal incontinence was calculated for each study by weighting the percentage change with the number of patients assessed at follow-up. In addition, sub-group analysis was conducted for PTQ and Durasphere bulking agents, comparing weighted mean percentage change in faecal incontinence over time (follow-up at six months or less versus follow-up of more than six months). The Fisher's combined probability test was used to evaluate the statistical significance of change in incontinence percentage for each time period. Unpaired t tests were used to assess statistical significance of change in incontinence percentage between different time periods. Statistical significance was deemed to be p<0.05. Data from studies were combined in a narrative synthesis.

Results of the review

Fourteen studies (n=420 patients, range 10 to 73) were included in the review: one randomised controlled trial (RCT) and thirteen case series. The RCT was reported to use concealed allocation, and blinded assessment of incontinence scoring. Of the case series, one scored 4 points, five scored 3 points, five scored 2 points and two scored 1 point. Follow up ranged from five weeks to 24 months.

Faecal incontinence (14 studies): One RCT (n=44 patients) reported no significant differences between PTQ injections and placebo at three months post-treatment. Eleven out of thirteen case-series studies reported improvement in incontinence scores at final follow-up (mean follow-up ranging from 1.5 months to 20.8 months). In sub-group analyses, no differences were reported between groups for PTQ and Durasphere injections for longer or shorter follow-up periods.

Anal manometry (nine case series): Two out of five case series using PTQ bulking agent reported a significant increase in maximum squeeze pressure, but not in maximum resting pressure. One of three case series using Durasphere injections reported significant increases in maximum squeeze pressure and maximum resting pressure. One case series reported no significant differences for either maximum squeeze pressure or maximum resting pressure using Contigen.

Quality of life (12 studies): One RCT (n=44 patients) found no statistically significant differences between PTQ injection and placebo. Seven out of 11 case series reported a statistically significant improvement in quality of life.

Adverse events and safety: Fifty-two adverse events were reported across the studies; most of these were considered minor. More serious events were persistent anal discomfort (n=1 patient), infection requiring drainage (n=1 patient), pain during defaecation (n=1 patient), and significant pain during injection (n=1 patient). Other events included anal bleeding, soiling, leakage and dermatitis. Migration of the injectable bulking agent was reported in 14 patients. Two patients reported leakage with stool.

Authors' conclusions

There was little evidence for the effectiveness of injectable bulking agents in managing passive faecal incontinence. The injectable bulking agents did appear to be safe, with only minor adverse events and no foreign body tissue reaction reported.

CRD commentary

The research question was clear with appropriate inclusion criteria. Several relevant sources were searched and attempts were made to reduce language bias. However, the inclusion of only published data meant that there may be some potential for publication bias. In addition, authors did not report end search dates, so it was unclear what time period this review covered. Appropriate methods were used to minimise reviewer error and bias in the review process.

Validity was assessed for case series using appropriate criteria and results were reported. Some details of validity were reported for the only RCT included in the review. A narrative synthesis was appropriate given the differences between studies in terms of study design, interventions, dosage and regimens. Few details were provided on participants, so it was not possible to judge the generalisability of the results. The authors appropriately commented on limitations within the review, including the small sample sizes and that most of the data were from case-series (prone to multiple biases). The authors also commented on the inability to obtain data from two completed but unpublished RCTs.

The authors' conclusions reflected the evidence presented, but the reliability of the conclusions is uncertain due to the poor quality evidence included in the review.

Implications of the review for practice and research

Practice: The authors stated that current evidence of the efficacy of PTQ bulking agent injections for managing passive faecal incontinence is weak. However, injectable bulking agents do appear to be safe with only minor adverse events and no foreign body tissue reaction reported.

Research: The authors stated that future research should include RCTs with large study populations and longer follow-up to provide higher quality evidence. In addition, the publication of unpublished evidence will improve the quality of evidence.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.